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Site-specific chemical modification of recombinant proteins produced in mammalian cells by using the genetically encoded aldehyde tag.


ABSTRACT: The properties of therapeutic proteins can be enhanced by chemical modification. Methods for site-specific protein conjugation are critical to such efforts. Here, we demonstrate that recombinant proteins expressed in mammalian cells can be site-specifically modified by using a genetically encoded aldehyde tag. We introduced the peptide sequence recognized by the endoplasmic reticulum (ER)-resident formylglycine generating enzyme (FGE), which can be as short as 6 residues, into heterologous proteins expressed in mammalian cells. Cotranslational modification of the proteins by FGE produced products bearing a unique aldehyde group. Proteins bearing this "aldehyde tag" were chemically modified by selective reaction with hydrazide- or aminooxy-functionalized reagents. We applied the technique to site-specific modification of monoclonal antibodies, the fastest growing class of biopharmaceuticals, as well as membrane-associated and cytosolic proteins expressed in mammalian cells.

SUBMITTER: Wu P 

PROVIDER: S-EPMC2651276 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature

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Site-specific chemical modification of recombinant proteins produced in mammalian cells by using the genetically encoded aldehyde tag.

Wu Peng P   Shui Wenqing W   Carlson Brian L BL   Hu Nancy N   Rabuka David D   Lee Julia J   Bertozzi Carolyn R CR  

Proceedings of the National Academy of Sciences of the United States of America 20090206 9


The properties of therapeutic proteins can be enhanced by chemical modification. Methods for site-specific protein conjugation are critical to such efforts. Here, we demonstrate that recombinant proteins expressed in mammalian cells can be site-specifically modified by using a genetically encoded aldehyde tag. We introduced the peptide sequence recognized by the endoplasmic reticulum (ER)-resident formylglycine generating enzyme (FGE), which can be as short as 6 residues, into heterologous prote  ...[more]

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